As part of our ongoing alternative medicine program, we have directed our attention toward the identification of edible seaweeds in Korea. Here we report on the anti-inflammatory activities of Ecklonia stolonifera. The present study was undertaken to elucidate the pharmacological and biological effects of E. stolonifera extracts on the production of inflammatory mediators in macrophages. The results indicate that the hexane fraction of E. stolonifera extract (ESH) is an effective inhibitor of lipopolysccharide (LPS)-induced NO, prostaglandin E2, and proinflammatory cytokine production in RAW 264.7 cells. These inhibitory effects of ESH were accompanied by decreases in the expression of inducible nitric oxide synthase and cyclooxygenase-2 proteins. Furthermore, ESH inhibited the LPS-induced phosphorylation and degradation of IκB-α, which is required for the nuclear translocations of the p50 and p65 nuclear transcription factor kappa-B (NF-κB) subunits in RAW 264.7 cells. Our results suggest that ESH might exert an anti-inflammatory effect by inhibiting the expression of pro-inflammatory cytokines. Such an effect is mediated by a blocking of NF-κB activation, which consequently inhibits the generation of inflammatory mediators in RAW264.7 cells. Through HPLC fingerprinting of the E. stolonifera extract, the phloroglucinol was also identified and quantified as standard substance. Moreover, we tested the potential application of E. stolonifera extract as a cosmetic material by performing human skin primary irritation tests. In these assays, E. stolonifera extracts did not induce any adverse reactions. Based on these results, we suggest that E. stolonifera extracts be considered possible anti-inflammatory candidates for topical application.